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Volume 16, Number 10, Issue of May 15, 1996 pp. 3427-3443
Copyright ©1996 Society for Neuroscience

Molecular Indices of Neuronal and Glial Plasticity in the Hippocampal Formation in a Rodent Model of Age-Induced Spatial Learning Impairment

Received Nov. 30, 1995; revised Feb. 20, 1996; accepted March 4, 1996.

Kiminobu Sugaya¹, Michael Chouinard¹, Rhonda Greene¹, Michael Robbins¹, David Personett¹, Caroline Kent¹, Michela Gallagher², and Michael McKinney¹

¹ Department of Pharmacology, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, and ² Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599

Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for -amyloid precursor protein (APP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of APP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (APP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and APP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.

Key words: cognition; spatial learning; messenger RNA; immunoblotting; in situ hybridization histochemistry; aging

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